Forkhead (FH) domain found in Forkhead box protein A2 (FOXA2) and similar proteins; FOXA2, also called hepatocyte nuclear factor 3-beta (HNF-3-beta or HNF-3B) or transcription factor 3B (TCF-3B), acts as a core transcription factor that controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis. It may also have an important role in bone metabolism. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 163 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 242
Cdd:cd20039    3 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 82

                         90       100
                 ....*....|....*....|..
gi 597518004 243 PDSGNMFENGCYLRRQKRFKCE 264
Cdd:cd20039   83 PDSGNMFENGCYLRRQKRFKCE 104

Forkhead N-terminal region; The region described in this family is found towards the N-terminus of various eukaryotic forkhead/HNF-3-related transcription factors (which contain the pfam00250 domain). These proteins play key roles in embryogenesis, maintenance of differentiated cell states, and tumourigenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004   23 SYYAEPEGYSSVSNMNAGLGMNGMNTYMSMSAAAMGGGSGNMSAGsmnMSSYVGAGMSPSlaGMSPGAGAMAGMSGSAGA 102
Cdd:pfam08430   1 SYYPEASESYSSVSGGMVYSMNSMNTYMPMNTMQTSTSSMNMSGY---AGPGAMNGMSSS--SMNGMSPGYGGAGSPMGM 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 597518004  103 AGVAGMGPHLSPS--LSPLGGQAAGAMGGLAPYANMNSMSPMYGQAGLSRARDPKTYRRSYTHA 164
Cdd:pfam08430  76 MGMSSMGTSLSPSgtMGAMGPQPAGSMGSLSPNQSMSRASNQYGQSNLNRARDPKTYRRSYTHA 139

Forkhead (FH) domain found in Forkhead box protein A2 (FOXA2) and similar proteins; FOXA2, also called hepatocyte nuclear factor 3-beta (HNF-3-beta or HNF-3B) or transcription factor 3B (TCF-3B), acts as a core transcription factor that controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis. It may also have an important role in bone metabolism. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 163 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 242
Cdd:cd20039    3 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 82

                         90       100
                 ....*....|....*....|..
gi 597518004 243 PDSGNMFENGCYLRRQKRFKCE 264
Cdd:cd20039   83 PDSGNMFENGCYLRRQKRFKCE 104

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004  165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPKDEPGKGSYWTIDPE 80

                  ....*.
gi 597518004  245 SGNMFE 250
Cdd:pfam00250  81 YEEMFE 86

HNF3 C-terminal domain; This presumed domain is found in the C-terminal region of Hepatocyte Nuclear Factor 3 alpha and beta chains. Its specific function is uncertain. The N-terminal region of this presumed domain contains an EH1 (engrailed homology 1) motif, that is characterized by the FxIxxIL sequence.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004  380 NHPFSINNLMsseqqhhhsHHHHQPHKMDLKAYEQVMHYPgGYGSPMPGSLAMG--PVTNKAGLDASPLAADTSYYQ 454
Cdd:pfam09354   1 NHPFSINNLM---------SSEQQHHKMDLKAYEQAMHYS-GYGSPMAGGLPMGssSVAGKSGLEPSAISPETSYYQ 67

DNA polymerase III subunits gamma and tau; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 266 QLALKEAAGAASSGGKKTAPGSQASQAQLGEAAGSASETPAGTESPHSSASPCQEHKRGGLSELKGAPASALSPPEPAPS 345
Cdd:PRK07764 386 GVAGGAGAPAAAAPSAAAAAPAAAPAPAAAAPAAAAAPAPAAAPQPAPAPAPAPAPPSPAGNAPAGGAPSPPPAAAPSAQ 465

                 ....*....
gi 597518004 346 PGQQQQAAA 354
Cdd:PRK07764 466 PAPAPAAAP 474

Forkhead (FH) domain found in Forkhead box protein A2 (FOXA2) and similar proteins; FOXA2, also called hepatocyte nuclear factor 3-beta (HNF-3-beta or HNF-3B) or transcription factor 3B (TCF-3B), acts as a core transcription factor that controls cell differentiation. It is a key transcriptional regulator that maintains airway mucus homeostasis. It may also have an important role in bone metabolism. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 163 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 242
Cdd:cd20039    3 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 82

                         90       100
                 ....*....|....*....|..
gi 597518004 243 PDSGNMFENGCYLRRQKRFKCE 264
Cdd:cd20039   83 PDSGNMFENGCYLRRQKRFKCE 104

Forkhead (FH) domain found in Drosophila melanogaster protein fork head (dFKH) and similar proteins; dFKH promotes terminal as opposed to segmental development. In the absence of dFKH, this developmental switch does not occur. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20041    1 KPPYSYISLITMAIQNSPNKMVTLSEIYQFIMDLFPFYRQNQQRWQNSIRHSLSFNDCFVKVPRTPDKPGKGSFWTLHPD 80

                         90
                 ....*....|....*...
gi 597518004 245 SGNMFENGCYLRRQKRFK 262
Cdd:cd20041   81 SGNMFENGCYLRRQKRFK 98

Forkhead (FH) domain found in Forkhead box protein A3 (FOXA3) and similar proteins; FOXA3, also called hepatocyte nuclear factor 3-gamma (HNF-3-gamma or HNF-3G), fork head-related protein FKH H3, or transcription factor 3G (TCF-3G), acts as an essential transcriptional regulator engaged in adipogenesis and energy metabolism. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 163 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 242
Cdd:cd20040    1 HAKPPYSYISLITMAIQQAPSKMLTLNEIYQWIMDLFPYYRENQQRWQNSIRHSLSFNDCFVKVARSPDKPGKGSYWALH 80

                         90       100
                 ....*....|....*....|..
gi 597518004 243 PDSGNMFENGCYLRRQKRFKCE 264
Cdd:cd20040   81 PNSGNMFENGCYLRRQKRFKLE 102

Forkhead domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004  165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:pfam00250   1 KPPYSYAALIAMAILSSPEKKLTLSEIYEWISENFPYYRTADKGWQNSIRHNLSLNKCFVKVPRPKDEPGKGSYWTIDPE 80

                  ....*.
gi 597518004  245 SGNMFE 250
Cdd:pfam00250  81 YEEMFE 86

Forkhead (FH) domain found in Forkhead box protein L1 (FOXL1) and similar proteins; FOXL1, also called Forkhead-related protein FKHL11 or Forkhead-related transcription factor 7 (FREAC-7), acts as a transcription factor required for proper proliferation and differentiation in the gastrointestinal epithelium. It may play a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 163 HAKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLH 242
Cdd:cd20027    1 PQKPPYSYIALIAMAIKSAPDQKVTLNGIYQFIMDRFPYYHDNKQGWQNSIRHNLSLNDCFVKVPREKGRPGKGNYWTLD 80

                         90
                 ....*....|....*...
gi 597518004 243 PDSGNMFENGCYLRRQKR 260
Cdd:cd20027   81 PDCEEMFENGNYRRRKRR 98

Forkhead (FH) domain found in the Forkhead box protein E (FOXE) subfamily; The FOXE subfamily includes two winged helix transcription factors, FOXE1 (also known as FOXE2) and FOXE3. FOXE1, also called Forkhead-related protein FKHL15, HFKH4, HNF-3/fork head-like protein 5 (HFKL5), or thyroid transcription factor 2 (TTF-2), is a transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. FOXE3, also called Forkhead-related protein FKHL12 or Forkhead-related transcription factor 8 (FREAC-8), is a transcription factor that controls lens epithelial cell growth through regulation of proliferation, apoptosis, and the cell cycle. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20019    1 KPPYSYIALIAMAIANSPERKLTLGGIYKFIMERFPFYRDNSKKWQNSIRHNLTLNDCFVKIPREPGRPGKGNYWTLDPA 80

                         90
                 ....*....|....
gi 597518004 245 SGNMFENGCYLRRQ 258
Cdd:cd20019   81 AEDMFDNGSFLRRR 94

Forkhead (FH) domain found in Forkhead box protein S1 (FOXS1); FOXS1, also called Forkhead-like 18 protein or Forkhead-related transcription factor 10 (FREAC-10), is a transcriptional repressor that suppresses transcription from the FASLG, FOXO3, and FOXO4 promoters. It may have a role in the organization of the testicular vasculature. It has also been implicated in energy turnover, motor function, and body weight. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20037    2 KPPYSYIALIAMAIQSSPGQRATLSGIYRYIMGRFAFYRHNRPGWQNSIRHNLSLNECFVKVPRDDRKPGKGSYWTLDPD 81

                         90
                 ....*....|....*..
gi 597518004 245 SGNMFENGCYLRRQKRF 261
Cdd:cd20037   82 CHDMFEHGSFLRRRRRF 98

Forkhead (FH) domain found in Forkhead box protein D4 (FOXD4) and similar proteins; FOXD4, also called Forkhead-related protein FKHL9, Forkhead-related transcription factor 5 (FREAC-5), or myeloid factor-alpha, is essential for establishing neural cell fate and for neuronal differentiation. The family also includes Forkhead box protein D4-like proteins, FOXD4L1-6. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20048    1 KPPYSYIALITMAILQSPHKRLTLSGICAFISGRFPYYRRKFPAWQNSIRHNLSLNDCFVKIPREPGHPGKGNYWSLDPA 80

                         90
                 ....*....|....*.
gi 597518004 245 SGNMFENGCYLRRQKR 260
Cdd:cd20048   81 SQDMFDNGSFLRRRKR 96

Forkhead (FH) domain found in Forkhead box (FOX) family of transcription factors and similar proteins; The FOX family comprises diverse tissue- and cell type-specific transcription factors with an evolutionary conserved "Forkhead (FH)" or "winged helix" DNA-binding domain. FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. The structure of the FH domain contains 2 flexible loops or "wings" in the C-terminal region, hence the term winged helix. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'. They participate in a variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism, and DNA damage response. Their expression can be regulated by multiple factors, and they can act as co-activators and/or transcriptional repressors. Fifty FOX-encoding genes in humans have been categorized into 19 subfamilies based on protein sequence homology (FOXA to FOXS).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 597518004 166 PPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWT 240
Cdd:cd00059    1 PPYSYAALIALAILSSPDKRLTLSEIYKWIEDNFPYYRTATKGWKNSIRHNLSLNKCFVKVPREPSDPGKGSYWT 75

Forkhead (FH) domain found in Forkhead box protein L2 (FOXL2) and similar proteins; FOXL2 is a transcriptional regulator that is essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Mutations in the FOXL2 gene cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I, a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II, the eyelid defect occurs as an isolated entity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20028    1 KPPYSYVALIAMAIRESPEKRLTLSGIYQYIIAKFPYYEKNKKGWQNSIRHNLSLNECFVKVPREGGGERKGNYWTLDPA 80

                 ....*...
gi 597518004 245 SGNMFENG 252
Cdd:cd20028   81 CEDMFEKG 88

Forkhead (FH) domain found in the Forkhead box protein C (FOXC) subfamily; The FOXC subfamily includes two winged helix transcription factors, FOXC1 (also called Forkhead-related protein FKHL7, or Forkhead-related transcription factor 3) and FOXC2 (also called Forkhead-related protein FKHL14, or Mesenchyme fork head protein 1). FOXC1 is a DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as the development of the eyes, bones, cardiovascular system, kidneys, and skin. FOXC2 acts as a transcriptional activator that might be involved in the formation of special mesenchymal tissues. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTL 241
Cdd:cd20017    1 KPPYSYIALIAMAIQNAPDKKITLNGIYQFIMDRFPFYRENKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTL 77

Forkhead (FH) domain found in Forkhead box proteins, FOXJ2, FOXJ3 and similar proteins; The FOXJ2-like subfamily includes two winged helix transcription factors, FOXJ2 and FOXJ3. FOXJ2, also called Forkhead homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. FOXJ3 is a transcription factor which regulates sperm function. It transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTL 241
Cdd:cd20024    1 KPPYSYATLITFAINSSPKKKMTLSEIYTWICENFPYYREAGTGWKNSIRHNLSLNKCFKKVPRSKDDPGKGSYWTL 77

Forkhead (FH) domain found in Forkhead box protein I1 (FOXI1) and similar proteins; FOXI1 is also called Forkhead-related protein FKHL10, Forkhead-related transcription factor 6 (FREAC-6), Hepatocyte nuclear factor 3 Forkhead homolog 3 (HFH-3), or HNF-3/fork-head homolog 3. It is a master regulator of vacuolar H-ATPase proton pump subunits in the inner ear, kidney, and epididymis, and is required for the development of normal hearing, sense of balance, and kidney function. Its epididymal expression is required for male fertility. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPD 244
Cdd:cd20053    4 RPPYSYSALIAMAIHGAPDKRLTLSQIYQYVADNFPFYNKSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTLDPN 83

                         90
                 ....*....|....*.
gi 597518004 245 SGNMFENGCYLRRQKR 260
Cdd:cd20053   84 CEKMFDNGNFRRKRKR 99

Forkhead (FH) domain found in the Forkhead box protein I (FOXI) subfamily; The FOXI subfamily includes three human winged helix transcription factors, FOXI1-3, Xenopus laevis FoxI1c, and similar proteins. FOXI1 acts as a transcriptional activator required for the development of normal hearing, sense of balance, and kidney function. FOXI2 may act as a transcriptional activator that plays a possible role in controlling cellular identity. Loss of function mutations in the FOXI2 gene may contribute to ectodermal dysplasia. FOXI3 plays a critical role in the development of the inner ear and jaw. It is a regulator of ectodermal development. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 597518004 166 PPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTL 241
Cdd:cd20025    1 PPYSYSALIAMAIQSAPEKKLTLSQIYQYVAENFPFYKRSKAGWQNSIRHNLSLNDCFKKVPRDEDDPGKGNYWTL 76

Forkhead (FH) domain found in the Forkhead box protein D (FOXD) subfamily; The FOXD subfamily includes four winged helix transcription factors, FOXD1-4. FOXD1, also called Forkhead-related protein FKHL8 or Forkhead-related transcription factor 4 (FREAC-4), is involved in transcriptional activation of Placental Growth Factor (PGF) and the complement component (C3) genes. It plays an important role in early embryonic development and organogenesis, and functions as an oncogene in several cancers. FOXD2, also called Forkhead-related protein FKHL17 or Forkhead-related transcription factor 9 (FREAC-9), is a probable transcription factor involved in embryogenesis and somatogenesis. FOXD3, also called HNF3/FH transcription factor genesis, acts as a transcriptional repressor that binds to the consensus sequence 5'-A[AT]T[AG]TTTGTTT-3'. It also acts as a transcriptional activator. It promotes development of neural crest cells from neural tube progenitors and restricts neural progenitor cells to the neural crest lineage while suppressing interneuron differentiation. FOXD3 is required for maintenance of pluripotent cells in the pre-implantation and peri-implantation stages of embryogenesis. FOXD4, also called Forkhead-related protein FKHL9 or Forkhead-related transcription factor 5 (FREAC-5), is essential for establishing neural cell fate and for neuronal differentiation. The family also includes Forkhead box protein D4-like proteins, FOXD4L1-6. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTL 241
Cdd:cd20018    1 KPPYSYIALITMAILQSPQKKLTLSGICEFIMNRFPYYREKFPAWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTL 77

Forkhead (FH) domain found in Forkhead box protein Q1 (FOXQ1) and similar proteins; FOXQ1, also called HNF-3/Forkhead-like protein 1 (HFH-1), or hepatocyte nuclear factor 3 Forkhead homolog 1, plays a role in hair follicle differentiation. It has also been reported to promote epithelial differentiation, inhibit smooth muscle differentiation, activate T cells and autoimmunity, and control mucin gene expression and granule content in stomach surface mucous cells. FOXQ1 is significantly associated with the pathogenesis of various tumor types including gastric, breast, colorectal, pancreatic, bladder and ovarian cancer, and glioma. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKP-GKGSFWTL 241
Cdd:cd20034    1 KPPYSYIALIAMAIRDSPSGRLTLAEINEYLMKKFPFFRGSYTGWRNSVRHNLSLNDCFVKVLRDPSRPwGKDNYWTI 78

Forkhead (FH) domain found in the Forkhead box protein F (FOXF) subfamily; The FOXF subfamily includes two winged helix transcription factors, FOXF1 and FOXF2, both of which are probable transcription activators for a number of lung-specific genes. FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins (ACD/MPV) suggest its involvement in ACD/MPV and lung organogenesis. FOXF2 is involved in programming organogenesis and regulating epithelial-to-mesenchymal transition (EMT) and cell proliferation. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 597518004 166 PPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHP 243
Cdd:cd20020    1 PPYSYIALIVMAIQASPTKRLTLSEIYQFLQQRFPFFRGPYQGWKNSVRHNLSLNECFIKLPKGLGRPGKGHYWTIDP 78

Forkhead (FH) domain found in Forkhead box protein J2 (FOXJ2) and similar proteins; FOXJ2, also called Fork head homologous X (FHX), plays an important role in tumorigenesis, progression, and metastasis of certain cancers. It acts as a transcriptional activator that can bind to two different type of DNA binding sites. It is specifically expressed in meiotic spermatocytes in adult mouse testes and appears to promote meiotic progression during spermatogenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 597518004 164 AKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTL 241
Cdd:cd20051    1 GKPPYSYATLITYAINSSPAKKMTLSEIYRWICDNFPYYRNAGVGWKNSIRHNLSLNKCFRKVPRPRDDPGKGSYWMI 78

Forkhead (FH) domain found in Forkhead box protein N2 (FOXN2) and similar proteins; The FOXN2-like group includes two FOXN subfamily winged helix transcription factors, FOXN2 and FOXN3. FOXN2, also called human T-cell leukemia virus enhancer factor (HTLF), is a potential tumor suppressor that can facilitate replication fork reversal. It acts as a transcription factor that binds to the purine-rich region in human T-cell leukemia virus long terminal repeat (HTLV-I LTR). It may be a potential therapeutic and radiosensitization target for lung cancer. FOXN3, also called checkpoint suppressor 1, acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKpGKGSFWT 240
Cdd:cd20031    1 KPPYSFSCLIFMAIESSPEKALPVKDIYSWIEKHFPYYRNAPSGWKNSIRHNLSLNKCFKKVEKEKNK-GKGSLWC 75

Forkhead (FH) domain found in Forkhead box protein K2 (FOXK2) and similar proteins; FOXK2, also called cellular transcription factor ILF-1 or interleukin enhancer-binding factor 1, is a transcriptional regulator that recognizes the core sequence 5'-TAAACA-3'. It binds to NFAT-like motifs (purine-rich) in the IL2 promoter. It also binds to the HIV-1 long terminal repeat. FOXK2 may be involved in both, positive and negative regulation of important viral and cellular promoter elements. In addition, FOXK2 plays a critical role in suppressing tumorigenesis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 164 AKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHP 243
Cdd:cd20055    2 SKPPYSYAQLIVQAITMAPDKQLTLNGIYTHITKNYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDP 81

                         90
                 ....*....|....*..
gi 597518004 244 DSGNMFENGCYLRRQKR 260
Cdd:cd20055   82 ASESKLIEQAFRKRRPR 98

Forkhead (FH) domain found in Forkhead box protein N3 (FOXN3); FOXN3, also called checkpoint suppressor 1 (CHES1), acts as a transcriptional repressor that may be involved in DNA damage-inducible cell cycle arrests (checkpoints). It displays transcriptional inhibitory activity, and is involved in cell cycle regulation and tumorigenesis. Alterations in FOXN3 are found in of a variety of cancers including melanoma, osteosarcoma, and hepatocellular carcinoma. FOXN3 also regulates hepatic glucose utilization/metabolism by regulating gluconeogenic substrate selection. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKP-GKGSFWTLHP 243
Cdd:cd20059    1 KPPYSFSCLIFMAIEDSPTKRLPVKDIYNWILEHFPYFANAPTGWKNSVRHNLSLNKCFKKVDKEKGQSiGKGSLWCIDP 80

                 .
gi 597518004 244 D 244
Cdd:cd20059   81 E 81

Forkhead (FH) domain found in Forkhead box protein K1 (FOXK1) and similar proteins; FOXK1, also called myocyte nuclear factor (MNF), acts as a transcriptional regulator that binds to the upstream enhancer region (CCAC box) of myoglobin genes. It positively regulates Wnt/beta-catenin signaling by translocating dishevelled (DVL) proteins into the nucleus. It also reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression. In addition, FOXK1 plays important roles in multiple human cancers. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 164 AKPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHP 243
Cdd:cd20054    2 SKPPYSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDP 81

                         90
                 ....*....|....*..
gi 597518004 244 DSGNMFENGCYLRRQKR 260
Cdd:cd20054   82 ASEAKLVEQAFRKRRQR 98

Forkhead (FH) domain found in Forkhead box protein P3 (FOXP3) and similar proteins; FOXP3, also called Scurfin, is a transcriptional regulator which is crucial for the development and inhibitory function of regulatory T-cells (Treg), which are required for maintaining self-tolerance. It may also have intrinsic regulatory function in conventional T (Tconv) cells. A deletion of the Forkhead domain arising from a frame-shift mutation in mouse FOXP3 is linked to the autoimmune disorder scurfy, and a similar congenital disease in humans is known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSpdkpgKGSFWTL 241
Cdd:cd20066    1 RPPFTYASLIRWAILESPEKQLTLNEIYHWFTRMFAFFRNNTATWKNAVRHNLSLHKCFVRVENE-----KGAVWTV 72

Forkhead (FH) domain found in Forkhead box protein P2 (FOXP2); FOXP2, also called CAG repeat protein 44, or Trinucleotide repeat-containing gene 10 protein, is a transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. It may also play a role in developing neural, gastrointestinal, and cardiovascular tissues. An arginine-to-histidine missense mutation (R553H) in the FOXP2 Forkhead domain has been linked to a severe speech and language disorder. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSpdkpgKGSFWTL 241
Cdd:cd20065    2 RPPFTYATLIRQAIMESSDRQLTLNEIYSWFTRTFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTV 73

Forkhead (FH) domain found in Forkhead box protein P1 (FOXP1); FOXP1, also called Mac-1-regulated Forkhead (MFH), is a transcription factor that is widely expressed and has a broad range of functions. It has been shown to have a role in cardiac, lung, and lymphocyte development. Deregulation of FOXP1 is an important contributor to the pathogenesis of diffuse large B-cell lymphoma (DLBCL), suggesting it may function as an oncogene. Loss of FOXP1 expression in breast cancer is associated with a worse outcome, suggesting that FOXP1 may function as a tumor suppressor in some tissues. Haploinsufficiency of the FOXP1 gene leads to a neurodevelopmental disorder termed FOXP1 syndrome, characterized by developmental delay, intellectual disability, autism spectrum disorder, speech delay, and dysmorphic features. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSpdkpgKGSFWTL 241
Cdd:cd20064    4 RPPFTYASLIRQAILESPEKQLTLNEIYNWFTRMFAYFRRNAATWKNAVRHNLSLHKCFVRVENV-----KGAVWTV 75

Forkhead (FH) domain found in the Forkhead box protein R (FOXR) subfamily; The FOXR subfamily includes two winged helix transcription factors, FOXR1-2. FOXR1, also called Forkhead box protein N5 (FOXN5), is required for proper cell division and survival possibly via the p21 and mTOR pathways. FOXR2, also called Forkhead box protein N6 (FOXN6), is an important player in a wide range of cellular processes such as proliferation, migration, differentiation, and apoptosis. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPG--KGSFWTLH 242
Cdd:cd20036    3 KPPLSYPNLIALALRNSETGSLNVQEIYDFIRFHFPFFRTAPDGWKNSVRHNLSFSDSFEKVPTSVSGYGgrRSCLWKLT 82

                 ..
gi 597518004 243 PD 244
Cdd:cd20036   83 PE 84

Forkhead (FH) domain found in Forkhead box protein O3 (FOXO3); FOXO3, also called AF6q21 protein or Forkhead in rhabdomyosarcoma-like 1 (FKHRL1), is a transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. It recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 169 SYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFLKVPRspDKPGKGSFWTLHP 243
Cdd:cd20061    5 SYADLITRAIESSPDKRLTLSQIYDWMVRCVPYFKdkgdsNSSAGWKNSIRHNLSLHSRFIRVQN--EGTGKSSWWMINP 82

                 .
gi 597518004 244 D 244
Cdd:cd20061   83 D 83

Forkhead (FH) domain found in Forkhead box protein O6 (FOXO6) and similar proteins; FOXO6 acts as a transcriptional activator that may play an important role on tumor invasion, metastasis and prognosis. The FH domain is a winged helix DNA-binding domain. All FOXOs bind to the consensus sequence 5'-GTAAACAA-3', known as the DAF-16 family member-binding element, which includes the core sequence 5'-(A/C)AA(C/T)A-3' recognized by all FOX family members.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 169 SYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYR-----QNQQRWQNSIRHSLSFNDCFLKVPRspDKPGKGSFWTLHP 243
Cdd:cd20063    4 SYADLITKAIESSPDKRLTLSQIYDWMVRYVPYFKdkgdsNSSAGWKNSIRHNLSLHTRFIRVQN--EGTGKSSWWMLNP 81

                 ....*
gi 597518004 244 DSGNM 248
Cdd:cd20063   82 EGGKT 86

Forkhead (FH) domain found in Forkhead box protein N1 (FOXN1); FOXN1, also called winged helix transcription factor nude, acts as a transcriptional regulator which regulates the development, differentiation, and function of thymic epithelial cells (TECs), both in the prenatal and postnatal thymus. It is also an important factor in controlling the skin wound healing process, as it actively participates in re-epithelialization and is responsible for scar formation. The FH domain is a winged helix DNA-binding domain. FOX transcription factors recognize the core sequence 5'-(A/C)AA(C/T)A-3'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 597518004 165 KPPYSYISLITMAIQQSPNKMLTLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVP-RSPDKPGKGSFWTLHP 243
Cdd:cd20056    2 KPIYSYSILIFMALKNSKTGSLPVSEIYNFMTEHFPYFKTAPDGWKNSVRHNLSLNKCFEKVEnKSGSSSRKGCLWALNP 81